WO2014083223A1 - Procédé d'obtention d'amines secondaires à partir de nitrobenzène dans un seul réacteur - Google Patents

Procédé d'obtention d'amines secondaires à partir de nitrobenzène dans un seul réacteur Download PDF

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Publication number
WO2014083223A1
WO2014083223A1 PCT/ES2013/070784 ES2013070784W WO2014083223A1 WO 2014083223 A1 WO2014083223 A1 WO 2014083223A1 ES 2013070784 W ES2013070784 W ES 2013070784W WO 2014083223 A1 WO2014083223 A1 WO 2014083223A1
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Prior art keywords
secondary amines
single reactor
reactor according
obtaining secondary
acid
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PCT/ES2013/070784
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English (en)
Spanish (es)
Inventor
Avelino CORMA CANÓS
Antonio LEYVA PÉREZ
Paula RUBIO MARQUÉS
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Consejo Superior De Investigaciones Científicas (Csic)
Universitat Politécnica De Valencia
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Publication of WO2014083223A1 publication Critical patent/WO2014083223A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
    • C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
    • C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the present invention relates to obtaining products of high industrial interest such as cyclohexylaniline and dicyclohexylamine, and substituted derivatives thereof, under mild reaction conditions using the industrial compound nitrobenzene and substituted derivatives thereof as the sole organic starting material. For this, it is necessary to prepare a supported palladium catalyst that allows the direct catalytic hydrogenation of nitrobenzene to the desired product depending on the quantity and dilution of the added aqueous acid, the hydrogen pressure, the amount of catalyst and the temperature of reaction.
  • the synthetic strategy described here is based on the use of a solid palladium catalyst that allows the cross-amination reaction between the aniline that is formed after the catalytic reduction of nitrobenzene and the cyclohexylamine that is formed after the reduction of the ring thereof, all under the same conditions of catalytic hydrogenation, resulting in the intermediate cyclohexylaniline, a product with industrial value (Xinhuan Yan; Fang Yang 2012, CN102531912, summary), in high yields.
  • cyclohexylaniline is produced with palladium or palladium-gold catalysts, under hydrogenating conditions and in the presence of an acidic function.
  • This new preparation strategy allows the process to be carried out in a single reactor, covering at least three synthetic elemental stages without the need to add or evacuate reagents during the process to selectively obtain secondary amines at the end of the process, for example cyclohexylaniline or dicyclohexylamine and its derivatives.
  • the present invention describes the direct obtaining of secondary amines, such as cyclohexylaniline, dicyclohexylamine and substituted derivatives thereof, starting with nitrobenzenes.
  • secondary amines such as cyclohexylaniline, dicyclohexylamine and substituted derivatives thereof.
  • nitrobenzenes generically referring to both the nitrobenzene compound and its derivatives.
  • nitrobenzene and its derivatives as nitro derivatives.
  • dicyclohexylamine can be obtained in high yield, after an increase in hydrogen pressure or reaction temperature.
  • the remaining aniline is recycled in the Synthesis reactor itself to form more cyclohexylaniline by coupled amination. Therefore, the entire process occurs in the same reactor, covering at least three synthetic elemental stages without the need to add or evacuate reagents during the process to selectively obtain secondary amines, for example cyclohexylaniline or dicyclohexylamine and derivatives thereof at the end of the process.
  • the present invention relates to a process for obtaining secondary amines from nitrobenzene and derivatives in a single reactor which may comprise introducing at least one nitrobenzene derivative, a solid catalyst, a solvent, an acid into a reactor. and hydrogen and that takes place in a single stage.
  • the nitrobenzene derivatives (s) used as the starting compound correspond to the formula.
  • R is selected from the group of linear or branched alkyls, the group of the esters, the group of the ethers and combinations thereof;
  • the catalyst used in the process described in accordance with the present invention is a catalyst comprising at least one support that can be selected from alumina, silica, carbon, amorphous aluminosilicates, crystalline aluminosilicates and combinations thereof, preferably carbon, and nanoparticles of at least one metal.
  • the nanoparticles can be nanoparticles of Pd, Ru, Pt, Rh, Ir, Pd-Au and combinations thereof.
  • the metal nanoparticles are preferably Pd nanoparticles, and more preferably Pd nanoparticles with an orientation ⁇ 100 ⁇ .
  • the metal nanoparticles are preferably Pd-Au nanoparticles.
  • m can be in a range between 1-20%, preferably between 1-5% by weight
  • n may be in a range between 0-20%, preferably between 0-5% by weight.
  • the metal 1 could be Pd and the metal 2 could be Au, the catalyst formula being as follows:
  • n can be in a range between 1-20%, preferably between 1-5% by weight, and n may be in a range between 0-20%, preferably between 0-5% by weight,
  • the catalyst used can be a supported palladium catalyst.
  • the palladium precursor is deposited, for example by impregnation with a solution of a palladium compound in a polar solvent, preferably ethanol.
  • a palladium precursor salts such as palladium ammonium nitrate, palladium chloride or palladium complexes such as palladium acetylacetonate or palladium acetate, among others, can be used.
  • the solution is prepared with the required amount and deposited on a solid support.
  • impregnation, precipitation or anchoring of the palladium precursor is used.
  • alumina preferably ⁇ -alumina
  • silica carbons
  • amorphous or crystalline aluminosilicates and combinations thereof can be used.
  • the precursor is reduced or calcined-reduced in order to obtain the supported palladium nanocrystals.
  • reducing agents H 2 , phenylethanol, sodium borohydride or any other reducer capable of reducing palladium at temperatures below 400 ° C can be used.
  • the orientation ⁇ 100 ⁇ is preferred.
  • the amount of Pd in the catalyst can be between 1-20% by weight.
  • the catalyst is a supported catalyst of palladium and gold.
  • the palladium and gold precursors are deposited, for example by impregnation with a solution of a palladium compound in a polar solvent, preferably ethanol.
  • a palladium precursor salts such as palladium ammonium nitrate, palladium chloride or palladium complexes such as palladium acetylacetonate or palladium acetate can be used.
  • a gold precursor salts such as gold chloride, gold bromide or sodium aurothiomalate can be used.
  • the solution is prepared with the required quantities and deposited on a solid support.
  • alumina preferably ⁇ -alumina
  • silica carbons
  • amorphous or crystalline aluminosilicates and combinations thereof can be used.
  • the precursors are reduced or calcined-reduced in order to obtain the supported palladium and gold nanocrystals.
  • reducing agents H 2 , phenylethanol, borohydride, or any other reducer capable of reducing palladium at temperatures below 400 ° C can be used.
  • the orientation ⁇ 100 ⁇ is preferred.
  • the amount of Pd in the catalyst can be between 1-20% by weight and between 0-20% by weight for gold.
  • the catalyst used in the present invention is a carbon supported palladium and gold catalyst that responds to formula (II)
  • the solid catalyst is produced after the co-hydrogenation of palladium and gold salts previously impregnated on the active carbon in aqueous solution.
  • This co-hydrogenation occurs by heating a gram of impregnated solid at 200 ° C for one hour under a flow of hydrogen of between 1 and 100 milliliters per minute, preferably between 5 and 10 milliliters per minute, diluted in nitrogen with a flow between 10 and 150 milliliters per minute, preferably between 90 and 120 milliliters per minute, and with a ramp of previous rise of between 5 and 20 ° C per minute until reaching the final temperature from ambient temperature.
  • the process of the present invention also includes the use of a solvent.
  • this solvent is selected from hexane, tetrahydrofuran, ether, dichloromethane, dioxane and combinations thereof, and more preferably from hexane, dichloromethane and combinations thereof.
  • said solvent is in an amount between 0.1-20 milliliters per millimol of nitro-derivative, and more preferably it is 10 milliliters per millimol of nitro-derivative.
  • those solvents that are not miscible with water are preferably used since they allow a good separation between solid catalyst and acid further favor the formation of secondary amines, for example cyclohexylaniline, dicyclohexylamine and derivatives, as is the preferred case of hexane and dichloromethane.
  • secondary amines for example cyclohexylaniline, dicyclohexylamine and derivatives, as is the preferred case of hexane and dichloromethane.
  • the acid used in the described process may be selected from hydrochloric acid, methanesulfonic acid, acetic acid, paratoluenesulfonic acid, an acid function forming part of the support and combinations thereof, and preferably is methanesulfonic acid.
  • reaction conditions according to the process of the present invention may vary. According to a particular embodiment, the reaction described is carried out at a temperature between 10 and 80 ° C, at a pressure between 5 and 20 atmospheres and for a time that can vary between one hour and five days (varying the time according to substrate) . By varying these reaction conditions it is possible to selectively obtain one product or another.
  • the process of the present invention is carried out in a batch reactor.
  • the product obtained is cyclohexylaniline and the reaction can be carried out at a temperature between 10 and 80 ° C, preferably between 14 and 60, and more preferably between 20-30 ° C, at a pressure between 5 and 20 atmospheres, preferably between 8-12 atmospheres, which is equivalent to an excess of between two and three times the amount required for the entire hydrogenation process.
  • the product obtained is dicyclohexylamine and the reaction can be carried out at a temperature between 10 and 80 ° C, preferably between 30 and 80, and more preferably between 50-80 ° C, at a pressure between 5 and 20 atmospheres, preferably between 10-15 atmospheres, which is equivalent to an excess of between two and three times the amount required for the entire hydrogenation process.
  • the representative molar ratio between nitrobenzene (starting material): catalyst: hydrogen: acid may vary in the range 100: 20-1: 800-200: 200-100, the preferred range being 100: 5: 600: 100.
  • Starting material means each molecule that contains a nitro group and a benzene ring, in the case of containing more than one of these groups the amounts should be recalculated accordingly.
  • the method described herein can also be used to couple two different nitro derivatives by adding in excess of the least reactive of them to favor heterocoupling instead of homocoupling in case the nitro derivatives are equal.
  • the product can be recovered after solid filtration and removal of volatile compounds from the rotary evaporator.
  • the solid thus recovered can be recycled for a second reaction.
  • Example 1 Preparation of palladium-gold on support.
  • Example 4 Preparation of cyclohexylaniline by hydrogen reduction of a solution of nitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • Example 5 Preparation of dicyclohexylamine by hydrogen reduction of a solution of nitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • Example 7 Preparation of N, N-p-tertbutylcyclohexyl p-terbutylaniline by hydrogen reduction of a solution of p-terbutyl nitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • Example 8 Preparation of Np-ethylcyclohexyl-p-ethylaniline by hydrogen reduction of a solution of p-ethylnitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • Example 9 Preparation of ethyl 4- (4- ((N- (p-methoxy-4-oxoethyl) cyclohexyl) amino) phenyl) butanoate by hydrogen reduction of a solution of ethyl p-nitrophenyl acetate in hexane using palladium supported and methanesulfonic acid.
  • Example 10 Preparation of 4- (4- ((N- (p-ethoxy-4-oxoethyl) cyclohexyl) amino) phenyl) ethyl acetate by hydrogen reduction of a solution of ethyl p-nitrophenyl acetate in hexane using palladium supported and methanesulfonic acid.
  • Example 11 Preparation of diphenethylamine ethyl acetate by hydrogen reduction of a solution of nitro-styrene in hexane using supported palladium and methanesulfonic acid.
  • Example 12 Preparation of bis- (4-methoxyphenethyl) amine by hydrogen reduction of a solution of p-methoxy-3-nitrostyrene in hexane using supported palladium and methanesulfonic acid.
  • Example 13 Preparation of N- (4-methoxyphenethyl) aniline by hydrogen reduction of a solution of p-methoxy- ⁇ -nitrostyrene and nitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • Example 14 Preparation of 2- (4- (p-tolylamino) phenyl) ethyl acetate by hydrogen reduction of a solution of ethyl p-nitrophenyl acetate in hexane using supported palladium and methanesulfonic acid.
  • Example 15 Preparation of bis (3,5-dimethylcyclohexyl) amine by hydrogen reduction of a solution of 1,3-dimethyl-5- nitrobenzene in hexane using supported palladium and methanesulfonic acid.
  • a reinforced glass reactor equipped with a pressure and temperature control, 30.5 mg (0.2 mmol) of 1,3-dimethyl-5- nitrobenzene is dissolved in the presence of 10 ⁇ (0.22 mmol) of methanesulfonic acid and 21 mg ( 5 mol%) of palladium on activated carbon, the reactor is purged 5 times with 10 bar of hydrogen, then filled with the desired pressure of H 2 (10 bar) and stirred at room temperature. During the experiment the pressure of H 2 is reduced. Aliquots are taken from the reactor at different times that are diluted in ethanol, centrifuged to remove catalyst particles and the product is analyzed with GC-MS. After 24 hours the conversion is 72%.
  • Example 16 Preparation of bis ((p-ethoxy-2-oxoethyl) cyclohexyl) amine by hydrogen reduction of a solution of ethyl p-nitrophenylacetate in hexane using supported palladium and methanesulfonic acid.
  • a reinforced glass reactor equipped with a pressure and temperature control
  • 41.8 mg (0.2 mmol) of ethyl p-nitrophenylacetate is dissolved in the presence of 10 ⁇ (0.22 mmol) of methanesulfonic acid and 21 mg of palladium on carbon active (5 mol%)
  • the reactor is purged 5 times with 10 bar of hydrogen, then filled with the desired pressure of H 2 (10 bar) and stirred at room temperature.
  • the pressure of H 2 is reduced.
  • Aliquots are taken from the reactor at different times that are diluted in ethanol, centrifuged to remove catalyst particles and the product is analyzed with GC-MS. After 24 hours the conversion is 72%.
  • Example 17 Preparation of indoline by hydrogen reduction of a Dissolution of ⁇ , 2-dinitro-styrene in hexane using supported palladium and methanesulfonic acid.
  • Example 18 Preparation of cyclohexylaniline by hydrogen reduction of a solution of nitrobenzene in hexane using supported palladium and acetic acid.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé d'obtention directe d'amines secondaires, comme par exemple de la cyclohexylaniline ou de la dicyclodihexylamine et des dérivés substitués de celles-ci, à partir de nitrobenzène et de dérivés dans un seul réacteur, lequel procédé est caractérisé en ce qu'il consiste à introduire dans ledit réacteur un dérivé de nitrobenzène, un catalyseur solide, un solvant, un acide et de l'hydrogène, et en ce qu'il est réalisé en une seule étape (one pot).
PCT/ES2013/070784 2012-11-30 2013-11-12 Procédé d'obtention d'amines secondaires à partir de nitrobenzène dans un seul réacteur WO2014083223A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP201231873 2012-11-30
ES201231873A ES2472344B1 (es) 2012-11-30 2012-11-30 Proceso de obtención de aminas secundarias a partir de nitrobenceno en un solo reactor

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WO2014083223A1 true WO2014083223A1 (fr) 2014-06-05

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107649184A (zh) * 2017-09-27 2018-02-02 武汉工程大学 一种灌流硅胶/纳米金复合微球及其制备方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1408530A (fr) * 1964-09-21 1965-08-13 Universal Oil Prod Co Procédé de préparation de cyclohexylamines nu-substituées par des hydrocarbures monocycliques
GB1235443A (en) * 1970-03-23 1971-06-16 Abbott Lab Process for making dicyclohexylamine
EP0211545A2 (fr) * 1985-08-01 1987-02-25 Imperial Chemical Industries Plc Procédé de réduction catalytique pour la production de composés aminés aromatiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1408530A (fr) * 1964-09-21 1965-08-13 Universal Oil Prod Co Procédé de préparation de cyclohexylamines nu-substituées par des hydrocarbures monocycliques
GB1235443A (en) * 1970-03-23 1971-06-16 Abbott Lab Process for making dicyclohexylamine
EP0211545A2 (fr) * 1985-08-01 1987-02-25 Imperial Chemical Industries Plc Procédé de réduction catalytique pour la production de composés aminés aromatiques

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A.T. MASSENOVA ET AL.: "Hydrogenation of aromatic nitro compounds on supported mono- and bimetallic catalysts", EURASIAN CHEMICO-TECHNOLOGICAL JOURNAL, vol. 2, no. 1, 2000, pages 101 - 105 *
C-H. TANG ET AL.: "Direct one-pot reductive N-alkylation of nitroarenes by using alcohols with supported gold catalysts", CHEMISTRY: A EUROPEAN JOURNAL, vol. 17, 2011, pages 7172 - 7177 *
DATABASE CHEMICAL ABSTRACTS 24 January 2014 (2014-01-24), accession no. 000:579815 *
H. ALPER ET AL.: "Catalytic reduction of the arene ring, and other functionalities, of organic substrates using formic acid and palladium over carbon", TETRAHEDRON LETTERS, vol. 33, no. 49, 1992, pages 7477 - 7480 *
P. RUBIO-MARQUES ET AL.: "A bifunctional palladium/acid solid catalyst performs the direct synthesis of cyclohexylanilines and dicyclohexylamines from nitrobenzenes", CHEM. COMMUN., vol. 49, no. 74, 2013, pages 8160 - 8162 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107649184A (zh) * 2017-09-27 2018-02-02 武汉工程大学 一种灌流硅胶/纳米金复合微球及其制备方法和应用

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ES2472344A1 (es) 2014-06-30

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